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WO1990006769A1 - Solution de perfusion antinephrotoxique - Google Patents

Solution de perfusion antinephrotoxique Download PDF

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Publication number
WO1990006769A1
WO1990006769A1 PCT/DE1989/000780 DE8900780W WO9006769A1 WO 1990006769 A1 WO1990006769 A1 WO 1990006769A1 DE 8900780 W DE8900780 W DE 8900780W WO 9006769 A1 WO9006769 A1 WO 9006769A1
Authority
WO
WIPO (PCT)
Prior art keywords
amino acids
mixture
kidney
use according
lsg
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DE1989/000780
Other languages
German (de)
English (en)
Inventor
Hagen Bertermann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SKREZEK CHRISTIAN
Original Assignee
SKREZEK CHRISTIAN
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by SKREZEK CHRISTIAN filed Critical SKREZEK CHRISTIAN
Priority to EP90900071A priority Critical patent/EP0408691B1/fr
Priority to DE58908288T priority patent/DE58908288D1/de
Priority to JP2500961A priority patent/JPH078790B2/ja
Priority to SU894830956A priority patent/RU2077883C1/ru
Publication of WO1990006769A1 publication Critical patent/WO1990006769A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes

Definitions

  • the toxic kidney damage represents a significant side effect of the cytostatic therapy of malignant tumors, which at the same time excludes about a third of the patients from the therapy.
  • further toxic damage to other organs, especially the bone marrow can occur if the renal elimination of the cytostatics or immunosuppressants is delayed.
  • Efforts to reduce toxicity by increasing diuresis and / or renal urine flow do not prevent serious disorders of kidney function due to the administration of cystostatics or immunosuppressants.
  • the renal deficiency often remains undetected clinically because the urinary substances in the blood only increase when the kidneys lose their function more radically.
  • the aim of the invention is to create a medicament which prevents damage to the kidney when cytostatic treatment of malignant tumors and when immunosuppressive agents are administered by blocking the mechanism of action of nephrotoxicity.
  • this object is achieved by the use of a mixture of L-amino acids which produces a modulation in the (protein) metabolism of the kidney cell, a mixture of glycine, alanine, serine, threonine, valine, leucine, isoleucine and Proline has proven to be suitable.
  • a formulation of the intravenous mixture in 8% aqueous solution has proven to be particularly suitable.
  • the mixture is preferably composed of 9-11 g / 1 glycine, 12-17 g / 1 alanine, 10-18 g / 1 serine, 2-5 g / 1 threonine, 5-10 g / 1 valine, 6-10 g / 1.
  • the amino acids can be dissolved in 0.45% saline solution, whereby the chloride of the saline solution can be partially replaced by aspartate with pH equilibration.
  • the mixture proposed here in the case of intravenous administration before the cytostatic treatment, causes toxic kidney damage caused by the cytostatic medication or when administering im- largely counteracts munsuppressiva.
  • the mixture proposed here stabilizes the renal filtration function and promotes the energy production of the tube cell during the early phase of kidney damage by cytostatics and immunosuppressants. This cellular point of attack of the mixture prevents the cell function loss leading to irreversible damage to the kidney cell with subsequent cell death.
  • the use proposed here is thus aimed at healthy kidneys who are at risk of kidney damage when treating another disease.
  • the kidney is not intended to be fed with the mixture proposed here, since this is otherwise ensured.
  • the exclusive toxicity block directed against toxic noxa minimizes the nitrogen load at the same time.
  • the protection effect depends on the concentration ratio of the amino acids used.
  • the proposed use of neutral L-amino acids for nephroprotective purposes is based on the modulation of intracellular autophagy in the kidney cell.
  • the activation of the autophagy system by nephrotoxic effects is reversibly blocked if the described L-amino acid mixture is applied beforehand.
  • the composition of the mixture is based on systematic studies on proximal tubular cells of the kidney.
  • the advantage of using a mixture consisting of different neutral amino acids is that they have a maximum effect in the cell What is achieved is that the individual L-amino acids of the mixture pass through the cell membrane via various transport channels and collect intracellularly. An intact kidney cell function proved to be an essential prerequisite for a successful toxicity blockade.
  • ITS Isolated proximal tubular segments
  • the ITS were suspended in an albumin-containing (10%) wrestling medium to which glucose (Gluc) and amino acids (AS) were added as substrates.
  • the leak rates of N-acetyl- ⁇ -D-glucosaminidase (NAG) observed in the reincubation period are assigned to the mitochondrial acceptor control index (ACI).
  • Cisplatin-free incubated ITS served as controls during the test.
  • Gluc 18 mM / 1
  • Gluc + AS 10 mM / 1 glucose + total 8 mM / 1 GLY, ALA, SER, THR, VAL, LEU, ILE, PRO.
  • kidney function measured. 12 patients each received either pretreatment with a nephroprotective amino acid mixture according to Table 2 (LSG II) or with a commercially available, conventional amino acid mixture (Table 3) (LSG I). x + SEM.
  • tubular N-acetyl-ß-D-glucosaminidase, NAG, based on grams of creatinine in urine
  • glomerular glomerular filtration rate

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Utilisation d'un mélange de différents acides L-amino pour protéger les reins des effets toxiques des produits cytostatiques et des immunosuppresseurs.
PCT/DE1989/000780 1988-12-22 1989-12-21 Solution de perfusion antinephrotoxique Ceased WO1990006769A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP90900071A EP0408691B1 (fr) 1988-12-22 1989-12-21 Solution de perfusion antinephrotoxique
DE58908288T DE58908288D1 (de) 1988-12-22 1989-12-21 Nephroprotektive infusionslösung.
JP2500961A JPH078790B2 (ja) 1988-12-22 1989-12-21 腎保護持続注入液
SU894830956A RU2077883C1 (ru) 1988-12-22 1989-12-21 Композиция для внутривенного введения для защиты почек от токсического действия нефротоксичных цитостатических средств и иммуносупрессоров

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP3843241.2 1988-12-22
DE3843241A DE3843241A1 (de) 1988-12-22 1988-12-22 Nephroprotektive infusionsloesung

Publications (1)

Publication Number Publication Date
WO1990006769A1 true WO1990006769A1 (fr) 1990-06-28

Family

ID=6369857

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1989/000780 Ceased WO1990006769A1 (fr) 1988-12-22 1989-12-21 Solution de perfusion antinephrotoxique

Country Status (8)

Country Link
EP (1) EP0408691B1 (fr)
JP (1) JPH078790B2 (fr)
AT (1) ATE110570T1 (fr)
AU (1) AU4807990A (fr)
DE (2) DE3843241A1 (fr)
ES (1) ES2063332T3 (fr)
RU (1) RU2077883C1 (fr)
WO (1) WO1990006769A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6875349B2 (en) 1996-05-24 2005-04-05 Cultor Corporation Method for fractionating a solution
US6896811B2 (en) 2001-05-09 2005-05-24 Danisco Sweeteners Oy Chromatographic separation method

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6096785A (en) * 1996-07-30 2000-08-01 Novartis Nutrition Ag Amino acid compositions and use thereof in treating renal dysfunction
UA65587C2 (en) * 1997-10-09 2004-04-15 Baker Norton Pharma Method for preventing nephrotoxicity induced by cyclosporins or tacrolimus
CN1191835C (zh) * 1999-02-23 2005-03-09 加利福尼亚大学董事会 嘧啶基核苷的制药用途
WO2003032949A1 (fr) 2001-10-19 2003-04-24 Isotechnika Inc. Nouveaux preconcentres en microemulsion d'analogues de cyclosporine
JPWO2005094813A1 (ja) * 2004-03-31 2008-02-14 味の素株式会社 腎疾患用薬剤
US9669010B2 (en) 2012-12-06 2017-06-06 Bio Health Solutions, Llc Treatment for chronic kidney disease
EP2928461B1 (fr) * 2012-12-06 2019-08-21 Bio Health Solutions, LLC Traitement pour maladie rénale chronique

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3414491A1 (de) * 1984-04-17 1985-10-24 Hans Dr. 8202 Bad Aibling Dietl L-aminosaeurengemische fuer die parenterale und orale anwendung bei nierenerkrankungen

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Band 111, Nr. 18, 30. October 1989, (Columbus, Ohio, US), siehe seite 423* zusammenfassung Nr. 160229v, & JP, A, 63307822 (Otsuka Pharmaceutical Co., Ltd) 15. Dezember 1988* *
PATENT ABSTRACTS OF JAPAN, Band 12, Nr. 237 (C-509) (3084), 6. Juli 1988; & JP-A-6330411 (Terumo Corp.) 9. Februar 1988 *
PATENT ABSTRACTS OF JAPAN, Band 12, Nr. 237 (C-509) (3084), 6. Juli 1988; & JP-A-6330413 (Terumo Corp.) 9. Februar 1988 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6875349B2 (en) 1996-05-24 2005-04-05 Cultor Corporation Method for fractionating a solution
US6896811B2 (en) 2001-05-09 2005-05-24 Danisco Sweeteners Oy Chromatographic separation method

Also Published As

Publication number Publication date
EP0408691A1 (fr) 1991-01-23
JPH03502805A (ja) 1991-06-27
DE58908288D1 (de) 1994-10-06
AU4807990A (en) 1990-07-10
ATE110570T1 (de) 1994-09-15
JPH078790B2 (ja) 1995-02-01
RU2077883C1 (ru) 1997-04-27
EP0408691B1 (fr) 1994-08-31
ES2063332T3 (es) 1995-01-01
DE3843241C2 (fr) 1990-11-22
DE3843241A1 (de) 1990-06-28

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